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ART for life cost effective for prevention of mother-to-child transmission in Uganda

Carole Leach-Lemens

Published: 18 September 2012

Combination antiretroviral therapy (ART)
provided to all pregnant women with HIV who have CD4 cell counts under 350
cells/mm3 (World Health Organization Option B) in Uganda
appears to be highly cost effective for the prevention of mother-to-child
transmission (PMTCT), even if continued over the mother’s lifetime, when compared
to single-dose nevirapine, two-drug therapy or no treatment, Andreas Kuznik and
colleagues report in a mathematical modelling study published in the August
edition of the Bulletin of the World
Health Organization.

Eighteen months of ART compared to single-dose nevirapine, dual therapy or no therapy
prevented 5.21, 3.22 and 8.58 disability-adjusted life years (DALYs),
respectively, with a corresponding incremental cost for each DALY averted of
US$46, US$99 and US$34.

DALYs
refer to the number of years of life saved in the Ugandan context assuming HIV
infection is prevented.

Uganda’s gross
domestic product (GDP) in 2009 was US$490 per person. The World Health Organization (WHO) considers a health
intervention cost effective and highly cost effective if the cost for each DALY
averted is less than three times the GDP and less than the GDP, respectively.

Sensitivity
analyses showed expanding treatment to include all eligible women currently
untreated appeared to be cost effective, assuming adherence does not fall below
40%.

The
only clinical outcome included in the analysis was mother-to-child transmission
of HIV. The authors did not look at how ART benefited maternal life expectancy
or take into account its mitigating effect on transmission to any uninfected
sexual partners of the mother. Consequently they believe their findings to be
conservative.

There are
approximately 12 million women with HIV in sub-Saharan Africa who are of childbearing age and,
each year, they account for an estimated 1.4 million pregnancies at risk for
mother-to-child transmission.

Uganda has the
second highest fertility rate in the world, of 6.7 children for each woman.
Approximately 91,000 infants are born each year to women with HIV. Barely
half of these women get any kind of PMTCT intervention. In 2009, mother-to-child
transmission accounted for approximately one in four of the 110,000 new HIV
infections in Uganda.

Of
those women who did get any antiretroviral drugs for PMTCT, close to 60%
received single-dose nevirapine while a quarter got dual therapy comprising
zidovudine and lamivudine for seven weeks and 17% got ART.

Following
the WHO 2010 PMTCT guidelines proposing programme options A and B, Uganda adopted
Option B in 2011. Once adequate resources are available all Ugandan health
facilities are expected to follow Option B.

The
authors believe this to be the first published study to look at the
cost-effectiveness of lifelong ART for PMTCT.

Having
developed a decision-based analytical model from the perspective of the Uganda national
health system, they looked at the cost-effectiveness of 18 months of ART for
PMTCT relative to other antiretroviral strategies for PMTCT (single-dose
nevirapine, dual therapy or no treatment); the cost-effectiveness of lifelong
ART and of expanding ART access to eligible untreated women.

Evaluation
of the cost-effectiveness of ART was based on the assumption ART reduces the
risk of transmission to the baby from 40% when the woman is not taking any treatment; to
25.8% with single-dose nevirapine (total drug cost US$0.06); to 17.4% with
dual therapy (US$15.63) and to 3.8% with ART for 18 months (total annual cost
US$469.77).

Lifelong
ART at a cost of US$6883 was anticipated to provide the same risk reduction in
each subsequent pregnancy.

Eighteen months of ART was calculated as highly cost effective, relative to other
therapies or no treatment, as follows: based on discounted differences in life expectancy between HIV-negative
(53.25 years) and HIV-positive children (less than two years without treatment;
14.23 years with ART) the authors estimated each child infection is associated
with 23.70 DALYs.

The
cost of ART for 18 months is US$482 for each person. The effect of ART in
reducing mother-to-child transmission is associated with cost offsets of US$240
and US$148 for each person relative to single-dose nevirapine and dual therapy,
respectively.

So
the total net incremental cost of ART for each pregnancy was estimated to be
US$242 (482-240) and US$318 (482-148) relative to single-dose nevirapine and
dual therapy, respectively. However, ART averts a mean of 5.21 DALYs and 3.22
DALYs relative to single-dose nevirapine and dual therapy, respectively.

So
the cost of ART for each DALY averted was approximately US$46 (US$242 divided
by 5.21) and US$99 (US$318 divided by 3.22) relative to single-dose nevirapine
and dual therapy, respectively.

Similarly
the incremental costs for each DALY averted because of lifelong ART are US$205,
US$354 and US$172 relative to single-dose nevirapine, dual therapy and no
treatment, respectively. The corresponding DALYs averted are 19.20, 11.87 and
31.60. However, lifetime ART being highly cost-effective is dependent upon the
assumed effectiveness of dual therapy, note the authors.

High
fertility rates are common in sub-Saharan Africa
yet only four countries have reached a target of 80% PMTCT coverage, so the
cost-effectiveness of lifelong ART will also depend on the number of future
childbirths for each woman.

The
authors believe their findings can be generalised to most countries in
sub-Saharan Africa.

Limitations
of the study include multiple trials rather than one randomised controlled
trial used for estimates of mother to child transmission rates. So differences
in demographics and study design may have influenced the results.

The
risk of transmission may vary according to the clinical stage of the maternal
HIV infection, whereas the authors used a constant transmission probability.

Pregnant
women in Uganda
usually present for antenatal care late in their pregnancy, after the fifth
month. ART may be less effective when started in the late stages of pregnancy. ART
is available in 109 out of 122 district hospitals. The authors suggest midwives
and other healthcare workers currently giving single-dose nevirapine or dual
therapy in these facilities could be trained to start ART, follow up patients
and link them to local and national programmes for HIV treatment and care.

Lack
of data meant the authors were unable to incorporate adherence into their
lifetime model. Given that their findings with 18 months of ART were sensitive
to adherence it would be more so for lifelong ART.

The
authors conclude “In Uganda ART appears highly cost-effective for PMTCT, even
if continued over the patients’ lifetimes. Given the additional public health
benefits of ART, efforts to ensure all HIV-positive women have access to
lifelong ART should be intensified.”

Reference

Kuznik A et al. Evaluating the cost-effectiveness of combination
antiretroviral therapy for the prevention of mother-to-child transmission of
HIV in Uganda. Online
edition Bull World Health Organ 90:565-603, doi:10.2471/BLT.11.095430, 2012.

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